Emerging encephalitis Nipah, Enterovirus 71, West Nile, and others … © by author O. Epaulard Department of Infectious Diseases ESCMID OnlineGrenoble Lecture University HospitalLibrary Unit of Virus - host cell interactions UMI 3265 UJF-EMBL-CNRS Declaration of interest • No contradictory interest © by author ESCMID Online Lecture Library Menu • General considerations • Flaviviruses West Nile virus • Henipaviruses © by author • Enterovirus 71 • ESCMIDHEV Online Lecture Library DNA viruses RNA viruses © by author ESCMID Online Lecture Library Hepeviridae Rubivirus Alphavirus Caliciviridae Flavivirus (HEV) (Rubella) (Chikungunya, O Nyong- (Norwalk) (YF, Dengue, JE, Nyong, Am. Eq. Enc.) WNV, TBE) Togaviridae Hepacivirus Enterovirus (HCV) (Coxsackie, echovirus, …) Flaviviridae Hepatovirus (HAV) picornaviridae Rabies Rhinovirus Rhabdoviridae Parechovirus RNA viruses Coronaviridae Morbillivirus Filoviridae (measles) (Marburg, Ebola) Paramyxoviridae© by author Orthomyxoviridae RubulavirusESCMIDPneumovirus OnlineBunyaviridae Lecture Library (mumps) (RSV) Henipavirus Retroviridae (Nipah, Hendra) Hantaviruses influenza Hepeviridae Rubivirus Alphavirus Flavivirus Caliciviridae (HEV) (Rubella) (Chikungunya, O Nyong- (Y (Norwalk) F, Dengue, JE, Nyong, Am. Eq. Enc.) TBE, WNV) Enterovirus Togaviridae Hepacivirus (Coxsackie, echovirus, …) (HCV) Hepatovirus Flaviviridae (HAV) picornaviridae Rhinovirus Rabies Rhabdoviridae Parechovirus RNA viruses Coronaviridae Morbillivirus Filoviridae (measles) (Marburg, Ebola) Paramyxoviridae© by author Orthomyxoviridae RubulavirusESCMIDPneumovirus OnlineBunyaviridae Lecture Library (mumps) (RSV) Henipavirus Retroviridae (Nipah, Hendra) Hantaviruses influenza Emerging diseases are mostly … • Viral • RNA • Zoonotic © by author • ESCMIDNo cross-immunity Online Lecture Library Why do infectious diseases emerge ? • Because they always have • Huge animal reservoir • Climate evolution • Air travel © by author • Urbanization • ESCMIDVirus mutation Online Lecture Library – Poor fidelity of polymerases of RNA viruses Did you mention bats ? • SARS-co • MERS-co • Nipah RNA viruses … • Hendra • Ebola © by author • Marburg • ESCMIDRabies Online Lecture Library Did you mention bats ? • SARS-co • MERS-co • Nipah • Hendra Drexler 2013 • Ebola © by author • Marburg • ESCMIDRabies Online Lecture Library © by author ESCMID Online Lecture Library Drexler 2013 Coronavirus in feces Astrovirus in feces © by author AdenovirusESCMID in feces Online Lecture Library Drexler 2013 Did you mention bats ? © by author ESCMID Online Lecture Library Smith 2013 © by author ESCMID Online Lecture Library Smith 2013 © by author ESCMID Online Lecture Library Flaviviruses Flaviviruses: highly successful Hepacivirus Pestivirus Flaviviridae © by author Flavivirus ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Flaviviruses: highly successful Dengue • From 9 to 100 countries concerned • 2,5 billions of people exposed • 50 to 100 millions cases a year, increasing • More explosive outbreaks • More northern© every by year author ESCMID– Including Europe Online Lecture Library © by author ESCMID Online Lecture Library Aedes albopictus in Europe (2012) © by author ESCMID Online Lecture Library Dengue Madeira 2012 © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library TBE © by author ESCMID Online Lecture Library ECDC datas © by author ESCMID Online Lecture Library ECDC datas © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library 2009 © by author ESCMID Online Lecture Library Duffy 2009 © by author ESCMID Online Lecture Library Zika fever in French Polynesia © by author ESCMID Online Lecture Library INVS datas August 1999, New York, New York • 2 then 8 then finally 59 cases of encephalitis in New York area © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library August 1999, New York, New York August 1999, New York, New York • 2 then 8 then finally 59 cases of encephalitis in New York area • First hypothesis : St Louis encephalitis – Because of outdoor activities of all patients – Serologic tests consistent • Concurrent outbreak© by in author crows – Including substantial crow death ESCMID Online Lecture Library – With encephalitis at necropsy August 1999, New York, New York • Final diagnosis of West Nile virus infection – In local crows – In a chilean flamingoe from a local zoo • Leading to the identification of the same virus in human cases© by author ESCMID Online Lecture Library Nash 2001 © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Roehrig 2013 © by author ESCMID Online Lecture Library May 2010 © by author ESCMID Online Lecture Library In USA : 16000 to 28000 patients 40% (?) neuro-invasive Roehrig 2013 1500 deaths © by author ESCMID Online Lecture Library Roehrig 2013 © by author ESCMID Online Lecture Library Petersen 2013 © by author ESCMID Online Lecture Library Petersen 2013 Meanwhile in Europe… 193 cases in 2013 © by author ESCMID Online Lecture Library 2010 163 cases 109 neuroinvasive infections © by author ESCMID Online Lecture Library 2011 West Nile virus • First isolated in Uganda, West Nile district, 1937 • Reservoir an amplificating host: birds – Mammals (including human) : dead-end • Viremia too weak© and by to authorshort • Vector:ESCMID mainly OnlineCulex mosquitoes Lecture Library © by author ESCMID Online Lecture Library Kramer 2008 © by author ESCMID Online Lecture Library Petersen 2013 © by author ESCMID Online Lecture Library Petersen 2013 West Nile virus fever • 25% of infected patient develop symptoms • In >50% of symptomatic patients : – Headache – Weakness – Rash (morbilliform/maculopapular) – Mild fever – Myalgia © by author • Less commonly : – Joint pain ESCMID– Eye pain Online Lecture Library – Vomiting/diarrhea – lymphadenopathy West Nile neuroinvasive diseases • 1/200 infected patients (1/10 symptomatic) – 1/50 in patients >65 yo – 1/800 in patients 16-24 yo – More frequent if cancer, diabetes, hypertension, alcohol abuse, renal disease • Abrupt onset © by author • Different forms ESCMID– Meningitis Online Lecture Library – Encephalitis – Acute flaccid paralysis © by author ESCMID Online Lecture Library Roehrig 2013 © by author ESCMID Online Lecture Library Petropoulou 2005 - Ali 2005 WNV infection diagnosis • Plasma serology • CSF serology • CSF PCR © by author ESCMID Online Lecture Library West Nile virus infection treatment • Treatment: only supportive – Ribavirin – Interferon α-2b – Polyclonal γ-globulins No effect – Neutralizing specific antibodies Antisens strategies – © by author • Preventive vaccines: ESCMID– Phases I and Online II (derived Lecture from equine Library vaccines) – No phase III © by author • Fatal encephalitis in a 10-y old boy of Powassan, ESCMIDOntario Online Lecture Library • Inoculation to newborn mice: encephalitis in 5d Powassan virus • Flavivirus related to TBE complex • Russia, Canada, USA – Imported from Russia ? In 1950s © by author • Zoonosis transmitted by ticks ESCMID– Dermacentor Online & Ixodes Lecture Library © by author ESCMID Online Lecture Library 2012 Powassan cases in the USA, 2001-2012 © by author ESCMID Online Lecture Library CDC datas Usutu virus © by author ESCMID Online Lecture Library Pauli 2014 Usutu virus • Birds cases © by author ESCMID Online Lecture Library Beck 2013 © by author ESCMID Online Lecture Library Usutu virus © by author ESCMID Online Lecture Library Other flavivirus encephalitis © by author ESCMID Online Lecture Library © by author • RecentlyESCMID considered Online to be theLecture same virus Library that Israel Turkey meningoencephalomyelitis virus © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Nipah (and Hendra) viruses • 265 cases / Fatality rate 40% • First supposed to be Japanese EV - but: – More adults than children – High attack rate – Several cases in the© householdby author • FirstESCMID viral isolate Online at Kampung Lecture Sungai Nipah Library (march 1999) • The outbreak was stopped after slaughtering 1.1 M pigs • 3 pig farmers • Clinics: – Fever, headache, altered consciousness – Dysautonomia / brainstem dysfunction – Hypotension and© death by author • Necropsy: ESCMID– Vasculitis-induced Online thrombosis Lecture Library – Viral inclusions in neurons – Cross-reactivity to Hendra Virus Nipah encephalitis virus • Natural host: pteropus bat • Tested positive in… – Cambodia – Thailand – Indonesia India – © by author – Madagascar ESCMID– Ghana Online Lecture Library Nipah encephalitis virus • Natural host: pteropus bat • Paramyxoviridae © by author ESCMID Online Lecture Library Nipah encephalitis virus • Natural host: pteropus bat • Paramyxoviridae • First documented cases: – Pigs in 1996 (retrospectively) • Transmission from bats • Due to modification/intensification of pig farming – Human in 1998© by author ESCMID– Cats, dogs, Onlinegoats… : dead-end Lecture Library Kulkarni 2013 Outbreaks in India & Bangladesh: 292 patients, 221 deaths © by author ESCMID Online Lecture Library Nipah virus transmission • Detectable in urine, feces, saliva • Malaysia, Singapore : – pig to human • At risk : pig farmers, pig slaughters • India, Bangladesh : – Bats to human © by author • Climbing to palm tree ESCMID• Drinking freshOnline date palm Lecture sap Library – Human to human • Including to HCW in hospital